Deena N. Pathak

Lipid Peroxidation and Glutathione Peroxidase, Glutathione Reductase, Superoxide Dismutase, Catalase, and Glucose‐6‐Phosphate Dehydrogenase Activities in FeCl3‐Induced Epileptogenic Foci in the Rat Brain

Summary: This study investigated the relationship between lipid peroxidation, subsequent activation of antiox‐idative enzymes, and development of iron‐induced epilepsy in the rat. Epileptic foci were produced in rat cerebral cortex by intracortical injection of ferric chloride (FeCl3). The epileptic foci were identified by electrocor‐ticography (ECoG). Epileptiform ECoG activity was shown to occur in the contralateral homotopic cerebral cortex as well. We measured levels of lipid peroxides and changes in the activities of the enzymes: superoxide dismutase (SOD), glutathione peroxidase (GP), glutathione reductase (GR), catalase (CA), and glucoses‐phosphate dehydrogenase (G6P) in the epileptogenic focus (both ipsilateral and contralateral) at days 3, 8, 15, and 23 after FeCI3 injection. Biochemical estimations were made in subcellular fractions, and changes in the ipsilateral site were compared with those in the contralateral site. The results of this study showed that large increases in lipid peroxidation were associated with development and buildup of the ECoG epileptiform discharges. Lipid peroxides increased in the ipsilateral focus by –100% as compared with control. In the contralateral site, however, the increase in lipid peroxides was marginal only. The increase in lipid peroxidation was concomitant with development of the high level of epileptiform activity. The time course of changes in lipid peroxidation paralleled the time course of development and persistence of the epileptiform activity. Regarding changes in the enzyme activities accompanying development of iron epilepsy, the data showed that although SOD and G6P increased by ˜60% and GR increased by ˜40%, the increases in the enzyme GP and CA were much lower, <20%. Thus, comparatively less increase in CA and GP activities produces a deficiency of these two enzymes in the iron (ipsilateral) focus. Among the various biochemical disturbances that have been identified as involved in epileptogenesis, peroxidative injury resulting from lipid peroxidation in neural plasma membrane may be causally related to development of paroxysmal epileptiform activity in the iron focus. Since GP is an enzyme of major importance in detoxification of lipid peroxides in the brain, based on the results presented in this article, it appears reasonable to suggest that GP deficiency causes lipid peroxidation to increase tremendously during iron epileptogenesis.

Effects of Chlorpromazine on the Activities of Antioxidant Enzymes and Lipid Peroxidation in the Various Regions of Aging Rat Brain

Abstract: In this work, the effect of chronic intraperitoneal administration of chlorpromazine (5 and 10 mg/kg) on the antioxidant enzymes superoxide dismutase (SOD), catalase (CA), glutathione reductase (GR), and glutathione peroxidase (GP); lipid peroxidation; and lipofuscin accumulation in the brains of rats ages 6, 9, and 12 months was studied. Chlorpromazine increased the activities of SOD, GR, and GP in particulate fraction from cerebrum, cerebellum, and brain stem in a dose‐dependent manner. While GR and SOD associated with soluble fraction increased, GP associated with soluble fraction was not affected. CA did not change after chlorpromazine administration in any regions of the brain of rats from all age groups. Chlorpromazine, thus, had a somewhat different action on antioxidant enzymes in different subcellular fractions. Chlorpromazine inhibited lipid peroxidation, both in vivo and in vitro, and it also inhibited accumulation of lipid peroxidation fluorescent products (lipofuscin), which was studied histochemically and biochemically as well. The data indicate that chlorpromazine inhibition of lipid peroxidation and of accumulation of lipofuscin can result from elevation of the activity of brain antioxidant enzymes.

Effect of centrophenoxine on the antioxidative enzymes in various regions of the aging rat brain

This study investigated the effect (in vivo) of centrophenoxine (Helfergin) on the activity of antioxidant enzymes (glutathione peroxidase GSH-PER, glutathione reductase GSSG-RED, superoxide dismutase SOD and catalase) in subcellular fractions from the regions of the brain (cerebrum, cerebellum and brain stem) of rats aged 6, 9 and 12 months. In all age groups, normal (control) activity of GSH-PER, GSSG-RED and SOD in the three brain regions was higher in the soluble fractions than in the particulate fractions. The three regions of the brain showed different levels of the enzyme activities. Enzymes in soluble fractions (except GSSG-RED in cerebrum of rats aged 12 months) did not change with age. In particulate fractions, however, the enzymes showed age-related changes: GSH-PER decreased with age in cerebellum and brain stem, but showed an age-related increase in cerebrum, GSSG-RED and SOD increased with age in all the three brain regions. Catalase activity in all the three brain regions remained unchanged in all age groups. Six week administration of centrophenoxine (once a day in doses of 80 mg/Kg and 120 mg/Kg) to the experimental animals produced increases in the activity of SOD, GSH-PER and GSSG-RED in particulate fractions from all the three brain regions. In the soluble fractions, however, only SOD and GSH-PER activity was increased. In vitro also centrophenoxine stimulated the activity of GSH-PER. A dosage of 80 mg/Kg produced greater changes than a 120 mg/Kg dosage. The drug had no effect on the activity of catalase. Centrophenoxine also reduced lipofuscin deposits (studied both biochemically and histochemically) thus indicating that the drug inhibited lipofuscin accumulation by elevating the activity of the antioxidant enzymes. The data suggest that alleviation of senescence by centrophenoxine may, at least, partly be due to activation by it of antioxidant enzymes.